Nanoparticles belong to a family of colloidal vectors which can be used, for example, for administering active ingredients, such as therapeutic molecules, in humans or animals. Such colloidal vectors preserve these active ingredients and can enable their controlled and/or sustained release at their site of action. Nanocapsules and nanospheres constitute two distinct groups of nanoparticles. Nanocapsules are formed from an aqueous or oily core coated with a polymeric membrane; nanospheres are formed from a polymeric matrix. The polymers which are part of the composition of nanoparticles are characterized by a high hydrophobicity (e.g. polyesters).
An aqueous suspension of polymeric nanocapsules is most commonly produced according to two techniques:                by interfacial polymer deposition (H. Fessi, F. Puisieux, J. P. Devissaguet, N. Ammoury, and S. Benita. Nanocapsule formation by interfacial polymer deposition following solvent displacement, International Journal of Pharmaceutics 55: R1-R4 (1989));        by emulsion-diffusion (D. Moinard-Checot, Y. Chevalier, S. Briancon, L. Beney, and H. Fessi. Mechanism of nanocapsules formation by the emulsion-diffusion process. Journal of Colloid and Interface Science In Press, Corrected Proof: 77).        
These two techniques require the use of organic solvents in order to dissolve the constitutive hydrophobic polymers of the polymeric membrane of the nanocapsules.
The technique of obtaining an aqueous suspension of polymeric nanoparticles by interfacial polymer deposition, which is the most common method for producing nanocapsules, is based on the deposition of preformed polymers at the interface between (i) an organic solvent mixed with an oil and (ii) an aqueous solution. In this process, a solution is prepared containing, e.g., an active ingredient in an organic solvent which is soluble or very soluble in water, such as acetone (with or without lipophilic surfactant). An oil which is miscible in the organic solvent but immiscible in water is added to the previous organic solution. The organic solution is then dispersed, by mechanical stirring, in the polar phase most commonly containing a hydrophilic surfactant (e.g., poloxamer, polysorbate 80). The organic solvent diffuses in the polar phase and this results in aggregation of the polymer around the lipid droplets responsible for the formation of the nanocapsules. The organic solvent can be dispersed in the polar phase by tangential membrane filtration followed by mechanical stirring (I. Limayem Blouza, C. Charcosset, S. Sfar and H. Fessi. Preparation and characterization of spironolacton-loaded nanocapsules for paediatric use International Journal of Pharmaceutics 325:124-131(2006)). The organic solvent is removed either by dialysis or, most commonly, by evaporation under reduced pressure.
The emulsion-diffusion technique (D. Moinard-Checot, Y. Chevalier, S. Briancon, L. Beney, and H. Fessi. Mechanism of nanocapsules formation by the emulsion-diffusion process. Journal of Colloid and Interface Science In Press, Corrected Proof: 77), for its part, consists in forming an emulsion in which the oily phase contains a biodegradable polymer and a partially water-miscible solvent (e.g., ethyl acetate, solubility: 8.3 g/100 ml at 20° C.) and or the polar phase containing an emulsifier is saturated with ethyl acetate. The addition of water to this emulsion causes diffusion of the solvent of the oil droplets toward the external phase, which leads to precipitation of the polymer around the oil droplets, and therefore the formation of nanocapsules. The organic solvent is removed either by dialysis or, most commonly, by evaporation under reduced pressure.
Consequently, the current methods for producing nanocapsules all comprise a preliminary step of dissolving the hydrophobic polymers in a mixture of one or more volatile organic solvents (e.g., acetone, ethyl acetate). The “spontaneous” formation of the nanocapsules is provided by the dispersion of the organic solutions of hydrophobic polymers in a polar mixture (e.g., most commonly aqueous solutions). The final production step requires evaporation under vacuum or dialysis of the organic solvents. The verification of the elimination of these solvents and the detection of possible traces thereof in the final preparation both constitute procedures which are lengthy and expensive and which require, on the industrial scale, the designing and setting up of complex infrastructures.